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National Whole Blood Summit 2019


jayinsat

Whole blood for Traumas  

26 members have voted

  1. 1. Are you currently considering using Low Titre O whole blood for traumas?

    • Yes
      5
    • No
      21

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  • Poll closed on 06/24/2019 at 06:28 PM

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Yesterday I attended the first of what I am sure to be many National Whole Blood Summits here in San Antonio.  https://strac.org/summit/

If your facility or trauma surgeons are not already pushing it, be prepared.  It is coming back.  The conferences was excellent.  The information and statistics presented was compelling.  Low Titre O whole blood is coming (back) and will be the preferred product in traumas and hemorrhagic shock.  Get ready!

Edited by jayinsat
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What is the rational for Whole blood vs. FFP and RBCs, especially with the blood mixers used at trauma bedside? Are there no problems with the decreased Coag factor levels with the older plasma in the WB units?  I know some trauma centers are using liquid plasma so there is no delay in response - is WB even better than that?  In what way?

What about platelets?  Do you still have to add them into the mix?

 

Edited by carolyn swickard
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No need for platelets if the whole blood is stored less than about 14-15 days.  Room temperature stored platelets aren't very effective in any case, particularly if ABO mismatched, and refrigerated whole blood platelets still retain some function for considerably longer than previously thought.  The main attraction for advocates is ease of use, as well as transportation simplicity to the site of traumatic injury.  There are those who believe that cold stored platelets will be more effective than the customary room temperature stored platelets.  There is no denying the first two points, but the third is still uncertain as far as clinical efficacy and safety.  That said, we've seriously overestimated the efficacy and seriously underestimated the toxicity of current platelet products (particularly those that are not ABO identical). Two recent randomized trials show that liberal platelet transfusion worsens bleeding and increases mortality compared with no transfusion or restrictive platelet transfusion.

Lancet. 2016 Jun 25;387(10038):2605-2613. doi: 10.1016/S0140-6736(16)30392-0. 

N Engl J Med. 2019 Jan 17;380(3):242-251. doi: 10.1056/NEJMoa1807320.

In addition to logistics, one major challenge is going to be the use of so-called universal donor O whole blood in the 55% of the population that is not group O.  If the whole blood is really low-titer (<50 or so) and only a few units are transfused, this practice is probably not likely to be a big problem for patients.  But we may see "indication creep," and use of group O whole blood (but not so low titer,  <200 :)) ) both in non-hospital situations and then in hospital treatment of patients of known ABO type (not O). This will potentially cause low grade hemolysis, bleeding, multi-organ failure and mortality if we are not careful about finding out what is both safe and effective (see references below). 

Fortunately for the advocates of whole blood, and hopefully, for our patients, the current practices of so-called "universal donor"group O red cells, whatever ABO type platelets and so-called "universal donor" AB plasma for all patients is highly toxic due to formation of ABO immune complexes in every patient we give this cocktail to.  Leads to hemolysis, endothelial cell injury, organ failure and increased bleeding in the patients we have reported, as compared with patients receiving only ABO identical transfusions.  Group O whole blood is ABO identical with 45% of recipients, which will be progress from 0% with our current protocols since 95% of recipients of AB plasma have antibody to the soluble antigen present.

My predicition is that If the amount of incompatible group O plasma from whole blood transfused is modest,  and the titer of anti-A/B is low enough, whole blood may indeed be safer than what we are currently transfusing. Time will tell.

Vox Sang. 2011 Jul;101(1):55-60. doi: 10.1111/j.1423-0410.2010.01464.x.

Anesth Analg. 2018 Jun;126(6):2135-2138. doi: 10.1213/ANE.0000000000002600.

Edited by Neil Blumberg
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1 hour ago, Neil Blumberg said:

Group O whole blood is ABO identical with 45% of recipients, which will be progress from 0% with our current protocols since 95% of recipients of AB plasma have antibody to the soluble antigen present.

My predicition is that If the amount of incompatible group O plasma from whole blood transfused is modest,  and the titer of anti-A/B is low enough, whole blood may indeed be safer than what we are currently transfusing. Time will tell.

What are you referring to with "95% of recipients of AB plasma have antibody to the soluble antigen present"?  

Even with low titer O Pos WB units aren't you going to see just as much formation of antigen-antibody complexes as you do with a non-type specific platelet pheresis?  The volume of plasma will be about the same and will contain anti-A, anti-B and anti-A,B,  correct?

What about the Trauma centers that are using A plasma - is that any better?

 

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Here is a link to excellent resources regarding studies and risks for Low Titre O Whole blood. https://www.strac.org/blood. I think this may help answer a lot of questions.

Here in San Antonio, I have seen great results from pre-hospital (ambulance and helicopter) use of cold-stored LTOWB.  Patients who have received units have arrived stable where, in the past, would have surely been an MTP activation.  Our local trauma centers are using it, up to 8 units before switching to components. The results have been positive. 

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What are you referring to with "95% of recipients of AB plasma have antibody to the soluble antigen present"?  

I'm referring to the unknown ABO type patient who receives AB plasma,  or the intentional use of AB plasma for all patients despite knowing the recipient's ABO type.  All of those O, A and B patients have antibody that will react with the A and B soluble antigens that are present in AB plasma (even in non-secretors, albeit in smaller amounts).  We and others have empirical and laboratory evidence that these immune complexes interfere with platelet and endothelial cell function/integrity leading to increased bleeding, lung injury, sepsis and mortality.

Even with low titer O Pos WB units aren't you going to see just as much formation of antigen-antibody complexes as you do with a non-type specific platvelet pheresis?  The volume of plasma will be about the same and will contain anti-A, anti-B and anti-A,B,  correct?

Don't know for sure, but a little bit of antibody in a body full of antigen may or may not be as dangerous as a little bit of antigen in the presence of lots of antibody (think about anaphylaxis versus the safety of IVIgG).  The biologic and clinical consequences of immune complex formation may well be dependent on ratios of antigen to antibody, and the size of the complexes formed. In general, lots of antibody on a bit of antigen seems to more biologically active than a lot of antigen with modest amounts of antibody.

What about the Trauma centers that are using A plasma - is that any better?

 

One of the first clues is that A plasma is no worse than AB, suggesting that the antibody content makes little difference. Group A plasma is at least identical with 40% of recipients.  Time will tell, but I suspect  that low titer O plasma and whole blood will be no worse than our current practices where we give tons of incompatible soluble antigen (and sometimes cellular antigen with platelets).

Edited by Neil Blumberg
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From Neil's post above:

"ABO type platelets and so-called "universal donor" AB plasma for all patients is highly toxic due to formation of ABO immune complexes in every patient we give this cocktail to"

Is there any data on this?  What ABO immune complexes are being formed from the transfusion of O pRBCs and AB plasma (which is the typical way to treat bleeding trauma patients)? 

Interesting concepts though, even though some of the "data" in these articles is a mixture of speculative opinion and retrospective study results from rather small cohorts.  It will be interesting to see how this progresses!

Scott

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Randomized trials from the 1990s show that clinical refractoriness (a death sentence pretty much) is two times higher when randomly selected ABO platelets are transfused (e.g., whatever is about to outdate) and five times higher when ABO incompatible are intentionally transfused. 

The rest of the data come from laboratory studies and observational clinical data.  ABO non-identical platelets are associated with 50% increases in red cell use in trauma patients and and 15% higher mortality rates.  In cardiac surgery, the receipt of two or more ABO non-identical platelets increases red cell transfusions by 50% and mortality by several fold compared with patients matched for the same number of ABO identical platelets.  ABO non-identical plasma is associated with significant increases in sepsis and acute lung injury in surgical patients, after adjustment for other prognostic factors. 

In vitro, ABO immune complexes cause hemolysis in group O red cells, interfere with platelet and endothelial cell function. 

If it walks like a duck and quacks like a duck, it's likely a duck :). 

We have all the knowledge we need to decide to stop prioritizing inventory management and prioritize not infusing incompatible ABO antigen and antibody, and it is feasible if you put your back into it in a larger hospital.  Harder for AB patients and smaller hospitals, but we can at least stop pretending that universal donor products are equivalent to ABO identical products in efficacy and safety.  They are not, even if we use them in emergencies. 

The references for all this (about a dozen studies) are in the Anesthesia and Analgesia paper listed above if anyone is interested.  The other issue is that those that reject  these conclusions have no data of their own to show that ABO non-identical platelets and other products are effective and safe, only expert opinion and historical habits of practice.

Edited by Neil Blumberg
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Dr. Blumberg, after all of your years of relentless pressure on this topic, I am finally starting to see it listed as a caveat to typical practice sometimes now so I think you are making some progress finally.  Still, it is so impossible at small, remote hospitals to both have sufficient platelets available and try to give ABO identical.  Will PAS platelets with less plasma help?  Also, I am hoping for 7 day outdates to ease some of the inventory pressure.  Maybe switching to whole blood for traumas will actually spare the platelet supply.  Also, all BB computers are set to flag plasma incompatible platelets only, not major incompatible.

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Does anyone know of a remote community hospital (~250 beds) that is using WB for traumas that is not a satellite hospital for a level 1 trauma center?  I just can't figure out the logistics for making the cost benefit ratio work here.  We are 3.5 hours' drive from our supplier, transfuse an average of one "real" massive transfusion patient a month (one that uses over 6 units of RBCs) and cover a land area the size of the Netherlands (as I recall).  The price for LTOWB is about 3X that of a RBC unit.  Would it do any good if our helicopter carried 2 units of whole blood even if we didn't keep it at any of our hospitals?

Also, can anyone share their QC process for packing the WB to packed cells once it is too old to use as WB?  You have to prove you get the right Hct at least a percentage of the time, correct?  Does the packing process require FDA registration?  It didn't use to.

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16 minutes ago, Mabel Adams said:

Does anyone know of a remote community hospital (~250 beds) that is using WB for traumas that is not a satellite hospital for a level 1 trauma center?  I just can't figure out the logistics for making the cost benefit ratio work here.  We are 3.5 hours' drive from our supplier, transfuse an average of one "real" massive transfusion patient a month (one that uses over 6 units of RBCs) and cover a land area the size of the Netherlands (as I recall).  The price for LTOWB is about 3X that of a RBC unit.  Would it do any good if our helicopter carried 2 units of whole blood even if we didn't keep it at any of our hospitals?

Also, can anyone share their QC process for packing the WB to packed cells once it is too old to use as WB?  You have to prove you get the right Hct at least a percentage of the time, correct?  Does the packing process require FDA registration?  It didn't use to.

Mabel, helicopter (and ambulance) use is the ideal place for LTOWB.  The main reason we are even considering its use is to cut down on wastage.  Without trauma center and other hospitals becoming a rotation site, LTOWB wastage can easily exceed 30%.  Like you, the cost is the reason we have not moved forward.

Edited by jayinsat
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I am a small hospital.  I was told by our blood supplier that when they provide LTOWB we will be contracted to order a set amount each month.  For example I would order 2 and they will arrive on the 15th of each month.  Now I use those 2 units on the 16th.  I cannot have anymore until the 15th of the next month.  This contract, and wastage encourages me not to provide this product, The same is true with liquid plasma.  Mabel I agree that maybe the LTOWB will alleviate platelet constraints in traumas.  I am hoping to see some more studies on the cold storage of platelets, I really hope this will be an acceptable practice in the future to extend the life of platelets.

Teresa

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On 5/24/2019 at 1:02 PM, TreeMoss said:

I think our major concern here is wastage.  However, our recent Level II Trauma inspector said that was probably not a valid reason not to start using whole blood!

Do you have a centrifuge?  You could spin it down and make CPD red cells and salvage plasma.

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On ‎5‎/‎31‎/‎2019 at 12:53 PM, jayinsat said:

Mabel, helicopter (and ambulance) use is the ideal place for LTOWB.  The main reason we are even considering its use is to cut down on wastage.  Without trauma center and other hospitals becoming a rotation site, LTOWB wastage can easily exceed 30%.  Like you, the cost is the reason we have not moved forward.

Back in the day when we had a whole blood inventory, we would just express the plasma from the red cells after they had settled out in the refrigerator without centrifuging. The theory was there was enough plasma left with the red cells and hematocrit wasn't too high.

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1 hour ago, sgrassley said:

Back in the day when we had a whole blood inventory, we would just express the plasma from the red cells after they had settled out in the refrigerator without centrifuging. The theory was there was enough plasma left with the red cells and hematocrit wasn't too high.

We still do this once and a while for autologous WB units.  But if you have to enter the unit to split it, then that cuts the outdate down to 24 hrs.  You would  have to be sure to have satellite packs for WB units.

As far as the "salvage plasma", you can simply fractionate it and use it for gamma globulin!

Scott

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"Will PAS platelets with less plasma help?"

Yes, the less incompatible antibody (group O mostly) and incompatible soluble and cellular antigen (group A mostly) in the transfusion the better.  Most toxicity in medicine is dose dependent, to state what everyone intuitively understands.  The ideal platelet product would be washed or otherwise plasma depleted group O platelets.  95% PAS platelets would come close and that's on the horizon.  Low titer group O platelets (<50 as for whole blood these days) would be better than what we are doing.  We should not let searching for perfection be the enemy of better practices.  As a large hospital transfusing 5-6,000 platelet doses (most of which are not indicated :) ) and with the capability of washing, we almost never give out platelets that aren't ABO identical or group O washed (or group A washed for AB patients) unless the ABO is unknown or it's an emergency.  Personally I'd rather wait for 2-12 hours for an ABO identical platelet than transfuse an ineffective and dangerous ABO mismanaged platelet in clinical situations that aren't massive transfusions.  The vast majority of our prophylactic transfusions provide no benefit except in acute myeloid leukemia induction therapy.  ABO mismatched transfusions actually make bleeding worse in many patients, so why urgently transfuse them to non-bleeding patients? It may cause bleeding, although I don't have that data in prophylactic transfusions.  Liberal platelet transfusion certainly caused bleeding in premature newborns who aren't bleeding in the recent randomized trial.

 

I realize our approach simply isn't possible in rural areas and for smaller hospitals.  A low titer group O platelet product or 95% PAS group O platelet product would provide greater efficacy and safety without question, but neither is currently available to my knowledge in the USA.  It's not rocket science, but for some reason, getting ABO safety right is a low priority for our field.  Our patients are the ones who are suffering increased bleeding, organ injury, hemolysis and mortality as the price.  The best you can do as a professional faced with these situations is try to get practitioners to defer transfusions for a few hours in non-bleeding patients and not release ABO mismatched platelets without warning the practitioner that this may cause bleeding or make existing bleeding worse.  You can cite our work and the work of other groups cited in our review above.  You have then discharged your duty and when things improve, as they will eventually, you won't have these unpleasant tasks.

Edited by Neil Blumberg
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We are a trauma-2 hospital in a reasonably populated area in mid-state Michigan.  Our hospital has 270 beds, and is busy with a number of neuro and CA patients, along with an open-heart program.  There are two other hospitals nearby who are also busy, but not nearly as busy as a big medical center like U of M in Ann Arbor.  So we have these utilization issues.  I wonder how many other hospitals have the same limitations.

We already have problems (like in December) of obtaining any platelets at times, much less ABO matched.  We normally only keep one 5-pack on hand for traumas, and we take what we can get, with the only exception being for females of child-bearing years.

Citations are not going to fix this no matter how good an idea it may be.

Scott

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"Citations are not going to fix this no matter how good an idea it may be."

Understood, but if the transfusion medicine leadership, AABB and FDA paid due attention to the data, blood centers would make available products such as plasma reduced group O platelets (whether PAS or washed or otherwise).  Or perhaps low-titer group O platelets. If they can do it for whole blood, they could do it for platelets to be used in rural areas and smaller hospitals that cannot inventory a range of products, and cannot wash on site.   Blood centers could produce something better than the current products that when used in non-O patients increase bleeding, organ injury and mortality.  But apparently, the old incorrect ideas, based upon assumptions that have been proven false,  hold sway despite the data.  If we ask for safer and more effective products, eventually someone will take the trouble to produce them. Right now, platelet transfusions as currently practiced produce more . harm than benefit.  It doesn't help that bedside practitioners have unrealistic expectations about efficacy and act as if this product was some sort of hemostatic glue rather than highly dysfunctional, activated cells that don't work very well and are quite toxic.

  

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Agree!  I am optimistic that as the data gets discussed more at various conferences and seminars, that we can move on to improvements on the supply side for those facilities who do not have the luxury of running their own donation service.

Scott

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On 6/1/2019 at 4:46 PM, Cliff said:

Do you have a centrifuge?  You could spin it down and make CPD red cells and salvage plasma.

I can't speak for other labs, but our 'large' centrifuges are big countertop models for specimen processing and the rotors won't accept the large buckets we would need to centrifuge a unit of blood (and none of them are refrigerated).  And quite frankly I wouldn't want to do it, even if I could, because of the contamination issue from processing specimens in that same centrifuge. I know we can sanitize, but yuck, just yuck.

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On ‎6‎/‎1‎/‎2019 at 3:46 PM, Cliff said:

Do you have a centrifuge?  You could spin it down and make CPD red cells and salvage plasma.

No, we don't have a centrifuge to spin blood down, and our FDA registration doesn't cover that -- although we could update that.

 

Anne

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2 hours ago, AMcCord said:

I can't speak for other labs, but our 'large' centrifuges are big countertop models for specimen processing and the rotors won't accept the large buckets we would need to centrifuge a unit of blood (and none of them are refrigerated).  And quite frankly I wouldn't want to do it, even if I could, because of the contamination issue from processing specimens in that same centrifuge. I know we can sanitize, but yuck, just yuck.

Aside from the "yuck" factor, centrifuges for WB are huge and generate massive G forces, a regular centrifuge would never work.

7 minutes ago, TreeMoss said:

No, we don't have a centrifuge to spin blood down, and our FDA registration doesn't cover that -- although we could update that.

 

Anne

Just an option.  Also, would your vendor take them back?

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19 hours ago, Cliff said:

Aside from the "yuck" factor, centrifuges for WB are huge and generate massive G forces, a regular centrifuge would never work.

Just an option.  Also, would your vendor take them back?

Yes, I imagine those centrifuges are still about the size of your average washing machine or bigger - not something I could find room for in our lab or our budget. When I first started in the lab business, won't say how long ago :rolleyes:, we did pack some cells (and wash platelets) using floor centrifuges with big buckets in Micro. That would never fly now! Talk about the "yuck" factor!!!

I haven't really investigated the WB option yet. I don't know if rotation would be an option or not. It isn't w/ 'liquid plasma, never frozen', so it might not be with WB. I suspect the WB product would be a special order situation. Will cross that bridge when/if I have to.

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